Diabetes is an international health concern with millions of patients worldwide. There is an unmet need to develop a biosensor technology that is a fast and convenient way to monitor blood glucose in diabetics. Thus, the particular goal of this research is the development of a self-cleaning hydrogel sensor membrane which undergoes cyclical, thermally driven removal of adhered cells to improve the efficacy and lifetime of an implanted glucose sensor. Implanted optically based sensors have the potential for continuous detection of an analyte (e.g. glucose). However, sensing is often compromised by the attachment and accumulation of cells from surrounding tissue as part of the host response. As a result, glucose diffusion is diminished and the sensor must be removed and replaced. We will develop novel self-cleaning thermoresponsive nanocomposite hydrogel membranes fabricated in the form of a hollow tube that houses a fluorescent glucose-responsive assay. The sensor will be implanted in the interstitial fluid just beneath the skin. After implantation, the glucose specific sensor will, when illuminated with the optical system developed, provide continuous measurement of fluorescence peaks that are proportional to the glucose concentration. There are three specific aims proposed in this research: (1) iteratively develop thermoresponsive nanocomposite hydrogel sensor membranes and characterize their mechanical properties as well as thermally-modulated swelling/dewelling behavior, surface hydrophilicity/- hydrophobicity, glucose diffusion and cell-release behavior, (2) iteratively evaluate the efficacy of selected thermoresponsive nanocomposite hydrogels sensor membranes to house a glucose-responsive assay, and (3) quantify the in vivo efficacy of the sensors prepared from selected self-cleaning hydrogel membranes containing the glucose-responsive assay, using both normal and diabetic rats. The facilities and individuals represented in this multidisciplinary team from the Biomedical and Chemical Engineering Departments at Texas A&M University are uniquely suited to carry out this research and have expertise in the chemical synthesis of thermoresponsive hydrogels, optical and electrochemical glucose biosensing, as well as biomedical and chemical engineering. The team has a history of collaboration and brings over 18 years of experience in the design and development of optical sensors for glucose and other analytes. PUBLIC HEALTH RELEVANCE: Diabetes mellitus is a debilitating, chronic, disease that affects over 180 million people, according to the World Health Organization, with estimates projecting to 366 million in 2030. The disease requires the patient to monitor glucose levels several times daily. This monitoring is currently non-continuous and performed primarily by using a commercially available finger or forearm stick method blood glucose reading device. Thus, the ultimate goal of this work is the development of an implantable self-cleaning glucose sensor that, once implanted, could be used to monitor glucose continuously with light from a watch-type of device to help patients with diabetes mellitus.